Comparison of Biomarker Modulation by Inhibition of EGFR and/or Src Family Kinases Using Erlotinib and Dasatinib in Head and Neck Lung Cancers

Trial Information

Comparison of Biomarker Modulation by Inhibition of EGFR and/or Src Family Kinases Using Erlotinib and Dasatinib in Head and Neck Lung Cancers

Background Head and neck squamous cell carcinoma (HNSCC) constitutes 3% of all malignancies
and is the sixth most common malignancy worldwide. There will be an estimated 40,000 new
cases and 11,000 deaths in the United States in 2007 and approximately 500,000 cases
worldwide yearly [1]. Squamous cell carcinoma accounts for at least 90% of all head and
neck cancers. Surgical resection remains a standard treatment for patients with resectable
HNSCC. For patients with high risk of local or distant relapse, radiation therapy (RT)
alone, or in combination with chemotherapy, is given after surgery to improve loco-regional
control and overall survival. Moreover, surgery often represents the only curative option in
patients who relapse locoregionally. Non-small cell lung cancer (NSCLC) is the leading cause
of death worldwide. NSCLC is infrequently diagnosed when the cancer can be eradicated with
surgical extirpation.

Specific Aims

- To determine the modulation of biomarkers by EGFR and/or Src targeting in head and neck
and lung cancers.

- To determine if biomarker modulation is associated with reduction of tumor volume
and/or evidence of histologic response in the tumor (e.g. decreased proliferation
and/or decreased apoptosis) as well as safety and tolerability.

Subject population Patients will be accrued from head and neck and lung cancer patients who
are surgical candidates. Surgery will be the primary curative treatment for patients
enrolled in this study. Patients should not require any standard induction treatment prior
to surgery. Surgery will have to be the best treatment option as determined by the treating
physician. Therefore, we will not be delaying chemoradiotherapy or other curative treatment.
We plan to include any stage of HNSCC or NSCLC that will be managed by primary surgery. If
surgery is unexpectedly cancelled, the patient will be removed from the study unless there
is an accessible lesion for biopsy. Ideally, the pre-treatment biopsy and the intraoperative
sample will be obtained from the same site (when there are multiple lesions). Please see
Section 3.0 for detailed eligibility criteria.

Treatment Plan The study drug or placebo will be taken for 14-21 days, and will be
discontinued one day prior to planned surgical resection. If surgery is delayed, the study
drug or placebo will be continued until one day prior to surgery, for up to a maximum of 28
days. Seven days is the minimum treatment for the patients to be evaluated. The interval
between the last dose of experimental drug and surgery will be 12-36 hours. Please see
Section 5.0 for treatment plan details. If the combination of erlotinib and dasatinib
results in toxicity leading to a delay in surgery, the study will be terminated.

Statistical design and sample size This is a 4-arm randomized trial that is intended to
estimate the effects of short-term preoperative therapy with EGFR and Src inhibitors upon a
panel of biomarkers. The 4 treatment arms are erlotinib, dasatinib, their combination, and a
placebo. We anticipate accruing 56 evaluable patients (14 patients per arm).

Inclusion Criteria:

- Histologically or cytologically confirmed, head and neck or lung cancers

- Any NSCLC histology is eligible. Stages I, II, IIIA (T3N1 only) or recurrent NSCLC
that will be managed with surgery are eligible.

- Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx)
or lung site will be included.

- Surgical resection of head and neck or lung must be planned, either as primary
treatment or salvage. Patients must have tissue available prior to receiving drug(s).

- Age greater then 18 years.

- ECOG performance status 0-2.

- Women of childbearing potential (WOCBP) must have:

1. A negative serum or urine pregnancy test within 72 hours prior to the start of
study drug administration

2. Persons of reproductive potential must agree to use and utilize an adequate
method of contraception throughout treatment and for at least 4 weeks after
study drug is stopped.

3. Ability to take oral medication (dasatinib must be swallowed whole).

4. Concomitant Medications

- Patients agrees to discontinue St. Johns Wort while receiving dasatinib therapy
(discontinue St. Johns Wort at least 5 days before starting dasatinib).

- Patient agrees that IV biphosphonates will be withheld for the first 8 weeks of
dasatinib therapy due to risk of hypocalcemia.

- Adequate hematologic, renal and hepatic function.

- Have signed written informed consent including a HIPPA form according to
institutional guidelines.

Exclusion Criteria:

- Subjects who fail to meet the above criteria.

- Prior therapy for head and neck or lung cancers is allowed, with the exception of
EGFR inhibitors. Any systemic therapy should have been completed at least 30 days
prior to study enrollment.

- Pregnancy or breastfeeding. Women (patients or partners of male patients) of
childbearing potential (WOCBP) must practice acceptable methods of birth control to
prevent pregnancy.

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